Advances in genomics offer the potential for novel clinical applications designed to identify individuals at greater susceptibility to cancer and develop personalized risk-reduction strategies. As such, the family history assessment is becoming increasingly important for cancer control and prevention. While significant advances have been made in our understanding of the etiology and clinical management in inherited colorectal cancer syndromes, such as familial adenomatous polyposis or hereditary non-polyposis colorectal cancer, most individuals with a family history of colorectal cancer do not have one of these well-described, Mendelian conditions. Our understanding of the mechanisms underlying the familial aggregation of colorectal cancers and the most effective screening strategies for individuals at increased risk for colorectal cancer remains limited. The long-term goals of Dr. Murff is to better delineate the complex genetic and environmental factors associated with familial colorectal cancer and translate these findings into improved management of high-risk individuals. The research aims of this proposal include: 1) To determine the effect of a family history of colon cancer on the initiation of colorectal cancer screening interventions; 2) To determine if an interaction exists between having affected relatives with colorectal cancer and patient lifestyle factors on adenoma risk; 3) To evaluate the relationship of functional genetic polymorphisms within the transforming growth factor beta signaling pathway to colonic adenoma risk and family colon cancer history; 4) To determine the cost-effectiveness of colorectal cancer screening in individuals at increased risk based on their family history. The early phases of this career development award will build on the candidate's prior work and determine current practices for cancer screening in high-risk individuals. Through the candidate's didactic coursework and mentorship plan, Dr. Murff will develop additional skills in genetics, cancer biology, and molecular epidemiology. The latter phases of the award will build on this new knowledge to investigate the genetic underpinnings of familial colon cancer. The experience gained from this career development award will ensure Dr. Murff's transition into an independent researcher in cancer epidemiology.